PB2489: ATAXIA LEADING TO A DIAGNOSIS OF PEDIATRIC CNS-ISOLATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN GRISCELLI SYNDROME TYPE 2
Authors: Surekha Tony, Roshan Mevada, Abdulhakim Al Rawas, Yasser Wali, Nawal Al Mashaykhi
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. Primarily characterized by a combination of partial albinism, hemophagocytic lymphohistiocytosis (HLH) or other immunodeficiency; neurological involvement at onset and its treatment in GS2 is rarely been described. Aims: We aim to present a rare case of a very young Omani girl with partial albinism presenting with ataxia as the sole manifestation, leading to the diagnosis of pediatric CNS-isolated HLH in GS2 in the absence of systemic HLH. Methods: We describe a 2.5-year-old girl with partial cutaneous albinism in an Omani family. She presented with acute ataxia after a brief period of progressive unsteady gait at onset with no history of fever or splenomegaly. There was a significant family history of two paternal cousins with a homozygous mutation in the FA2H gene confirming the diagnosis of spastic paraplegia type 35 (SPG35). Both these cousins had presented at 2 years of age with gait instability. MRI brain revealed acute inflammation of cerebellum and brain stem with high signal intensities in the cerebellar white matter and medulla, cerebellar edema with crowded posterior fossa, caudal tonsillar displacement and medulla oblongata wrapped by tonsils in foramen magnum. IV pulse Methylprednisolone was initiated for 5 days in an attempt to decrease the inflammation on the cerebellum and brainstem. Infectious and metabolic work up were negative. In view of the strong family history of spastic paraplegia and clinical features of partial cutaneous albinism, whole exome sequencing was done. Results: A homozygous variant in the RAB27A gene was identified confirming the diagnosis of autosomal recessive Griscelli syndrome type 2. Bone marrow aspirate revealed trilineage representation with evidence of hemophagocytosis. CSF analysis revealed pleocytosis with mature lymphocyte but no hemophagocytosis. Biochemical parameters for HLH were negative. Patient was treated with weekly intra thecal chemotherapy (IT Methotrexte, and IT hydrocortisone) and started on steroids as per HLH 1994 protocol without Etoposide in order to minimize toxicity, as she was planned for urgent HSCT. Simultaneously she was closely monitored for splenomegaly and biochemical parameters of HLH. Follow-up MRI showed overall improvement of signal in the cerebellar hemispheres dominantly white matter. Patient is in a good condition with significant improvement in ataxia and scheduled for HSCT. Summary/Conclusion: We report an atypical form of GS2 manifesting as severe central nervous system involvement at onset with HLH. This case highlights the need for early consideration of immunologic and genetic evaluation for HLH and GS2 in patients with unexplained neuro-inflammation, especially in the presence of partial albinism.Keywords: Hemophagocytic Lymphohistiocytosis (HLH)